Stanford Health Now

Rewriting Immunity's Rules: New Strategies Against Cancer

Albert Yu came through months of treatment that gave him a new immune system. Now, two years after the transplant that fought his cancer, he and his wife, Mary Bechmann Yu, are living a life renewed.

Watch 68-year-old Albert Yu's vigorous swing of a tennis racket and
it's hard to imagine that he is the veteran of some tough years of
chemotherapy and radiation, the kind often prescribed to beat back
cancer. He plays with determined control and balance, keeping up even
when he's challenged by a steady stream of machine-fed balls.

Just two years ago, Yu could barely get up out of a chair. He was at
the end of an exhausting eight years of battle against lymphoma.
That's a cancer that hits white blood cells and distorts their ability
to protect the body from bacteria and disease. His physicians at
Stanford Hospital had used the most advanced therapies available, even
enrolling Yu in clinical trials of experimental treatments. The cancer
would go away for a little bit, Yu said, then it would come back. It
became more and more obvious, said his wife, Mary Bechmann Yu,
"that the remissions were getting shorter and shorter and that we
needed to rethink our strategy."

Replacing Yu's exhausted immune system with a transplant was the
avenue his Stanford physicians suggested, a version of a whole system
do-over first accomplished in 1956 by replacing a patient's diseased
bone marrow with healthy marrow from his identical twin. The bone
marrow is where the body generates cells for the immune system. Over
the decades, the transplant technique has been improved to make
transplants possible between unrelated people. But the underlying
challenge has remained the same: to provide a new immune system that
recognizes the abnormality of cancer cells and destroys them while
accepting the cells in its new body, just if they were original equipment.

Tricking immune cells

Albert Yu played tennis before he became ill with cancer and, since his bone marrow transplant, he's worked diligently to get back his game.

His Stanford physicians offered Yu a new treatment called, for short,
TLI/ATG. The letters represent a two-part approach to manipulating the
behavior of the immune system. The regimen is based on a discovery
made by Stanford immunologist Samuel Strober, MD.

The TLI/ATG strategy, initially developed through animal studies,
relies on the impact of radiation on certain cells in the immune
system. Strober observed that those cells could be manipulated with
radiation to increase in number and to do a better job of attacking
cancer cells. The other trick in the strategy is to reduce the
reaction of the transplanted immune cells to their new environment.
Typically, they would attack, in a behavior called graft versus host
disease, but the TLI/ATG protocol suppresses that response.

"It's a wonderful example of bench to bedside research,"
said Robert
Lowsky, MD, who worked with Strober, Judy Shizuru,
MD, PhD, and other Stanford physicians to perfect the treatment
they first saw work with mice in 2001. Yu read about the technique in
2005 and was intrigued because it offered someone like him, then
beyond the standard age for transplant, a chance for a more sustained
remission. "It was a higher risk," he said, "but a
higher return."

Cellular transplants began at Stanford in 1986, with a bone marrow
transplant for a child with leukemia. Since then, more than 3,800
adults and children have been treated. The program, with a 22-bed
adult inpatient unit at the Hospital and 56-bed/chair outpatient
infusion area, is recognized by the National Cancer Institute for its
excellence in care and research.

Scientific advances pushed a change in the program's name from
"Bone Marrow" to "Blood and Marrow." The staff now
includes a cadre of more than 50 nurses specially certified in
oncology and chemotherapy. Some have been with the program since its
inception. The program also includes collaborative care rooms so
patients with cardiac issues can receive that extra layer of required attention.

"You get to know everybody there," Yu said, "and
after a while, they're like family."

Preparing at home

For months, Yu had to be careful about his activities, especially those that exposed him to other people and possible infection. Now, his new immune system is strong.

Yu's treatment protocol allowed him to be physically conditioned and
then transplanted almost completely without hospitalization, in
comparison to the weeks of isolation behind double doors that some
transplant patients must endure. But the treatment still requires
juggling a complex set of interconnected events designed to push his
immune system down to zero while keeping him from becoming infected.
He was vulnerable to even one stray germ, his wife said. "It was
a little bit like walking a tightrope and he was so fragile."

Yu said his wife made an extraordinary effort to make their home a
totally clean place. They also asked to consult with someone who'd
gone through the same procedure. Stanford made that introduction.
Hearing about the experience first-hand, said Mary Bechmann Yu,
"turned out to be a tremendous resource, medically and emotionally."

When, finally, Yu sat in a reclining chair at Stanford's Cancer
Center so the transplant cells could flow through an IV into his arm,
it was almost a non-event, Yu said. "They just bring in a bag and
injected it into my vein. But it was very emotional for me. I felt
somebody gave me life."

The BMT program found Yu a donor who was a perfect match. Future
patients will benefit from work that continues to modulate treatment
even further so those immune system cells can be even more precisely
controlled, said Robert Negrin,
MD, Chief of the Division of Blood and Marrow Transplantation.
"There's a lot going on now to try to understand and figure out
what controls the induction of an immune response—how these cell
populations talk to each other." Then comes the issue of how to
use that knowledge to predict an individual's unique interaction to
chemotherapy, radiation and transplanted donor cells.

The hope, Lowsky said, is to be able to manipulate the immune system
to accept any donated cell or tissue, enabling any patient to have a
transplant that would not trigger rejection.

Regaining power

Over the next nine months, as his new immune system built its
ability to function at full strength, Yu took life slowly. Every day,
he went to the Cancer
Center where nurses would draw his blood, test it and give him
additional treatments. "Then I'd receive whatever was needed that
day to try to normalize my blood chemistry," Yu said, "and
keep me going while I healed and until I could make immune cells on my own."

The BMT program hosts an annual reunion for its patients; this group, photographed at this year's gathering, represents some of those who've had their transplants 10 years.

The TLI/ATG protocol produces such a long-lasting impact on the
immune system that Yu does not need additional daily medication to
suppress his immune system. He has also worked to regain his muscle
tone and cardiovascular stamina, enrolling in an exercise class and
working out with weights. In addition to tennis, he's also swimming
and playing golf.

"I feel that once you've had cancer, I don't think you want to
say you can be cured for sure. On the other hand, there's no point in
thinking about it," Yu said. "We're way more conscious about
how we spend our time," said his wife. "We have a very
different yardstick to our calendar."

SPECIAL FEATURE

What to know about blood and marrow transplantation

Bone marrow, the liquid center of our bones, produces red blood cells that carry oxygen, platelets that control bleeding and white blood cells, the vital part of our infection-fighting immune system. Inserting donated bone marrow builds a new immune system able to eliminate various kinds of cancers, including leukemia and lymphoma.

Bone marrow can be withdrawn under regional or general anesthesia from the hip bones, but most donations of immune system-generating blood cells can be taken directly from the blood stream.

After donation, a person's marrow is replenished within four to six weeks.

To join the national registry, donors must be between 18 and 60 years old.

The closer the match between donor tissue and patient, the better. Genetics determine tissue type, so the more complex someone's ethnic makeup, the more difficult it is to find a donor.

The non-profit National Marrow Donor Program has been registering and connecting donors with patients since 1987. It now includes 7 million donors and works with a group of almost 500 hospitals, blood centers and laboratories. It is also part of a worldwide network that works cooperatively with service organizations, student groups and corporations to build the registry.

CARE AT STANFORD

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